title: Determination of the detectable concentration of manganese used in neuronal MEMRI and its effect on cortical neurons in vitro.
abstract: OBJECTIVE
  Manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) has received increasing attention because of its functional and anatomic value in brain studies. However, the contrast agent, Mn(2+), will lead to neurotoxicity at high concentrations, which limits its use in biomedical research. This study was designed to determine whether Mn(2+) can significantly enhance the signal intensity (SI) of primary cultured cortical neurons at non-toxic levels.
  
  
  METHODS
  Neurons were incubated with different concentrations of Mn(2+) (control and 0.01, 0.05, 0.10, and 0.20 mM), then a cellular MRI was performed in vitro and the intracellular Mn(2+) concentrations were analyzed by ICP-MS. At the same time, the cell viability, LDH release assay, intracellular ROS level, and apoptosis were measured 24 h after treatment.
  
  
  RESULTS
  (1) After the neurons were treated with Mn(2+) at a low concentration (0.01 mM), there was no impact on cell viability and cytotoxicity, and no significant signal was enhanced on MEMRI. (2) When the neurons were exposed to higher concentrations of Mn(2+) (0.05, 0.1, and 0.2 mM), a significant increase in signal quality was achieved, but cell viability was significantly reduced and the intracellular ROS formation and percentage of TUNEL-positive cells were increased significantly.
  
  
  CONCLUSIONS
  At Mn(2+) concentrations > 0.05 mM, significant enhancement of MEMRI SI occurred, but with overt cytotoxicity.
authors.affiliation: Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Run
authors.initials: R
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Fanheng
authors.initials: F
authors.lastname: Huang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Fa
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D003287:Contrast Media / Q000032:analysis / Q000633:toxicity; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D042541:Intracellular Space / Q000737:chemistry / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008345:Manganese / Q000032:analysis / Q000633:toxicity; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D003287:Contrast Media; D017382:Reactive Oxygen Species; D008345:Manganese